Heme Oxygenase Active-Site Residues Identified by Heme−Protein Cross-Linking during Reduction of CBrCl3†

Biochemistry ◽  
1998 ◽  
Vol 37 (9) ◽  
pp. 2889-2896 ◽  
Author(s):  
Angela Wilks ◽  
Katalin F. Medzihradszky ◽  
Paul R. Ortiz de Montellano
Keyword(s):  
Heme Oxygenase ◽  
Active Site ◽  
Heme Protein ◽  
Cross Linking ◽  
Active Site Residues ◽  
Protein Cross Linking

Structural and Dynamic Repercussions of Heme Binding and Heme−Protein Cross-linking inSynechococcussp. PCC 7002 Hemoglobin†

Biochemistry ◽  
2006 ◽  
Vol 45 (47) ◽  
pp. 14075-14084 ◽  
Author(s):  
David A. Vuletich ◽  
Christopher J. Falzone ◽  
Juliette T. J. Lecomte
Keyword(s):  
Heme Protein ◽  
Cross Linking ◽  
Heme Binding ◽  
Protein Cross Linking

scholarly journals Site-Specific, Intramolecular Cross-Linking of Pin1 Active Site Residues by the Lipid Electrophile 4-Oxo-2-nonenal

2015 ◽  
Vol 28 (4) ◽  
pp. 817-827 ◽  
Author(s):  
Christopher D. Aluise ◽  
Jeannie M. Camarillo ◽  
Yuki Shimozu ◽  
James J. Galligan ◽  
Kristie L. Rose ◽  
...  
Keyword(s):  
Active Site ◽  
Cross Linking ◽  
Active Site Residues ◽  
Site Specific

Transglutaminases: Protein Cross-Linking Enzymes in Tissues and Body Fluids

1994 ◽  
Vol 71 (04) ◽  
pp. 402-415 ◽  
Author(s):  
Daniel Aeschlimann ◽  
Mats Paulsson
Keyword(s):  
Body Fluids ◽  
Cross Linking ◽  
Protein Cross Linking

Tridegin, a Novel Peptidic Inhibitor of Factor XIIIa from the Leech, Haementeria ghilianii, Enhances Fibrinolysis In Vitro

1997 ◽  
Vol 77 (05) ◽  
pp. 0959-0963 ◽  
Author(s):  
Lisa Seale ◽  
Sarah Finney ◽  
Roy T Sawyer ◽  
Robert B Wallis
Keyword(s):  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Factor Xiiia ◽  
Cross Linking ◽  
Fibrinolytic Enzymes ◽  
Small Polypeptide ◽  
Tissue Plasminogen ◽  
Protein Cross Linking

SummaryTridegin is a potent inhibitor of factor Xllla from the leech, Haementeria ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated fibrin degradation as shown by the absence of D-dimer and approximately halves the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse more rapidly when either streptokinase, tissue plasminogen activator or hementin is added 2 h after clot formation. The effect of Tridegin is markedly increased if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is present, the rate of lysis returns almost to that of platelet- free clots. These studies indicate the important role of platelets in conferring resistance to commonly used fibrinolytic enzymes and suggest that protein cross-linking is an important step in this effect. Moreover they indicate that Tridegin, a small polypeptide, may have potential as an adjunct to thrombolytic therapy.

Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A

2017 ◽  
Vol 14 (10) ◽  
pp. 1122-1137 ◽  
Author(s):  
Nivedita Singh ◽  
Parameswaran Saravanan ◽  
M.S. Thakur ◽  
Sanjukta Patra
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Signal Transduction Pathway ◽  
Docking Study ◽  
Primary Objective ◽  
Cgmp Level ◽  
Active Site Residues ◽  
Aromatic Fragment ◽  
Docking Approach ◽  
Free Energy Of Binding

Background: Phosphodiesterases 9A (PDE9A) is one of the prominent regulating enzymes of the signal transduction pathway having highest catalytic affinity for second messenger, cGMP. When the cGMP level is lowered, an uncontrolled expression of PDE9A may lead to various neurodegenerative diseases. To regulate the catalytic activity of PDE9A, potent inhibitors are needed. Objective: The primary objective of the present study was to develop new xanthine based inhibitors targeting PDE9A. This study was an attempt to bring structural diversification in PDE9A inhibitor development because most of the existing inhibitors are constructed over pyrazolopyrimidinone scaffold. Methods: Manual designing and parallel molecular docking approach were used for the development of xanthine derivatives. In this study, N1, N3, N9 and C8 positions of xanthine scaffold were selected as substitution sites to design 200 new compounds. Reverse docking and pharmaceutical analyses were used for final validation of most promising compounds. Results: By keeping free energy of binding cut-off of -6.0 kcal/mol, 52 compounds were screened. The compounds with substitution at N1, N3 and C8 positions of xanthine showed good occupancy in PDE9A active site pocket with a significant interaction pattern. This was further validated by screening different factors such as free energy of binding, inhibition constant and interacting active site residues in the 5Å region. Substitution at C8 position with phenyl substituent determined the inhibition affinity of compounds towards PDE9A by establishing a strong hydrophobic - hydrophobic interaction. The alkyl chain at N1 position generated selectivity of compounds towards PDE9A. The aromatic fragment at N3 position increased the binding affinity of compounds. Thus, by comparative docking study, it was found that compound 39-42 formed selective interaction towards PDE9A over other members of the PDE superfamily. Conclusion: From the present study, N1, N3 and C8 positions of xanthine were concluded as the best sites for substitution for the generation of potent PDE9A inhibitors.

scholarly journals Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces

2021 ◽  
Author(s):  
Yixuan Xie ◽  
Siyu Chen ◽  
Qiongyu Li ◽  
Ying Sheng ◽  
Michael R Alvarez ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sialic Acid ◽  
Membrane Proteins ◽  
Cell Membranes ◽  
Sialic Acids ◽  
Cross Linking ◽  
Protein Networks ◽  
Cell Surfaces ◽  
Protein Cross Linking

A cross-linking method is developed to elucidate the glycan-mediated interactions between membrane proteins through sialic acids. The method provides previously unknown extensive glycomic interactions on cell membranes. The vast majority...

scholarly journals An enzymatic activation of formaldehyde for nucleotide methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charles Bou-Nader ◽  
Frederick W. Stull ◽  
Ludovic Pecqueur ◽  
Philippe Simon ◽  
Vincent Guérineau ◽  
...  
Keyword(s):  
Amino Acids ◽  
Thymidylate Synthase ◽  
Active Site ◽  
De Novo ◽  
Crystallographic Structure ◽  
De Novo Synthesis ◽  
Active Site Residues ◽  
Enzymatic Activation ◽  
Enzyme Cofactors ◽  
Unique Ability

AbstractFolate enzyme cofactors and their derivatives have the unique ability to provide a single carbon unit at different oxidation levels for the de novo synthesis of amino-acids, purines, or thymidylate, an essential DNA nucleotide. How these cofactors mediate methylene transfer is not fully settled yet, particularly with regard to how the methylene is transferred to the methylene acceptor. Here, we uncovered that the bacterial thymidylate synthase ThyX, which relies on both folate and flavin for activity, can also use a formaldehyde-shunt to directly synthesize thymidylate. Combining biochemical, spectroscopic and anaerobic crystallographic analyses, we showed that formaldehyde reacts with the reduced flavin coenzyme to form a carbinolamine intermediate used by ThyX for dUMP methylation. The crystallographic structure of this intermediate reveals how ThyX activates formaldehyde and uses it, with the assistance of active site residues, to methylate dUMP. Our results reveal that carbinolamine species promote methylene transfer and suggest that the use of a CH2O-shunt may be relevant in several other important folate-dependent reactions.

Sign in / Sign up

Export Citation Format

Share Document